Claims
- 1. A compound of the formula I ##STR44## in which: R(1), R(2) and R(3)
- independently of one another are --Y-{4-R(8)-phenyl}, --Y-{3-R(8)-phenyl} or --Y-{2-R(8)-phenyl},
- where the phenyl in each case is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, --CF.sub.3, methyl, hydroxyl, methoxy and --NR(96)R(97);
- R(96) and R(97)
- independently of one another are hydrogen or --CH.sub.3 ;
- Y is a bond, CH.sub.2, oxygen, --S-- or --NR(9);
- R(9) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
- R(8) is SO.sub.a {NR(98)}.sub.b NR(99)R(10);
- a is 1 or 2;
- b is 0 or 1;
- a+b=2;
- R(98), R(99) and R(10)
- independently of one another are hydrogen, --(C.sub.1 -C.sub.8)-alkyl, benzyl, --(C.sub.2 -C.sub.8)-alkylene-NR(11)R(12), (C.sub.2 -C.sub.8)-alkylene-NR(13)--(C.sub.2 -C.sub.8)-alkylene-NR(37)R(38) or (C.sub.0 -C.sub.8)-alkylene-CR(39)R(40)--CR(41)--R(42)(C.sub.0 -C.sub.8)-alkylene-NR(43)R(44);
- R(11), R(12), R(13), R(37), R(38), R(43) and R(44)
- independently of one another are hydrogen, --(C.sub.1 -C.sub.8)-alkyl or benzyl;
- R(39), R(40), R(41) and R(42)
- independently of one another are hydrogen, --(C.sub.1 -C.sub.8)-alkyl or --(C.sub.0 -C.sub.3)-alkylenephenyl,
- where the phenyl is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, --CF.sub.3, methyl and methoxy; or
- R(99) and R(10)
- together are 4-6 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, --S--, --NH--, --NCH.sub.3 or --N-benzyl; or
- R(8) is SO.sub.a {NR(98)}.sub.b NR(95)--C{.dbd.N--R(94)}--NR(93)R(92);
- R(92), R(93), R(94) and R(95)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3) independently of one another are
- pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl,
- which are unsubstituted or substituted by 1-4 substituents selected from the group consisting of F, Cl, Br, I, --CN, (C.sub.2 -C.sub.8)-alkanoyl, (C.sub.2 -C.sub.8)-alkoxycarbonyl, formyl, carboxyl, --CF.sub.3, methyl, and methoxy; or
- R(1), R(2) and R(3)
- independently of one another are hydrogen, --(C.sub.1 -C.sub.8)-alkyl, --(C.sub.2 -C.sub.8)-alkenyl or --(CH.sub.2).sub.m R(14);
- m is zero, 1 or 2;
- R(14) is --(C.sub.3 -C.sub.8)-cycloalkyl or phenyl,
- which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, --CF.sub.3, methyl, methoxy and --NR(15)R(16);
- R(15) and R(16)
- are hydrogen or --CH.sub.3 ; or
- R(1), R(2) and R(3)
- independently of one another are --Q4{(CH.sub.2).sub.k --CHR-(17)--(C.dbd.O)R(20)}-phenyl, --Q-3-{(CH.sub.2).sub.k --CHR(17)--(C.dbd.O)R(20)}-phenyl or --Q-2-(CH.sub.2).sub.k --CHR(17)--(C.dbd.O)R(20)}-phenyl,
- where the phenyl in each case is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, --CF.sub.3, methyl, hydroxyl, methoxy and --NR(35)R(36);
- R(35) and R(36)
- independently of one another are hydrogen or --CH.sub.3 ;
- Q is a bond, oxygen, --S-- or --NR(18);
- R(18) is hydrogen or --(C.sub.1 -C.sub.4)-alkyl;
- R(17) is --OR(21) or --NR(21)R(22);
- R(21) and R(22)
- independently of one another are hydrogen, --(C.sub.1 -C.sub.8)-alkyl, --(C.sub.1 -C.sub.8)-alkanoyl, --(C.sub.1 -C.sub.8)-alkoxycarbonyl, benzyl, or benzyloxycarbonyl; or
- R(21) is trityl;
- R(20) is --OR(23) or --NR(23)R(24);
- R(23), R(24) independently of one another are hydrogen, --(C.sub.1 -C.sub.8)-alkyl or benzyl;
- k is zero, 1, 2, 3 or 4; or
- R(1), R(2) and R(3)
- independently of one another are (C.sub.1 -C.sub.9)-heteroaryl,
- which is linked via C or N and which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino; or
- R(1), R(2) and R(3) are
- --SR(25), --OR(25), --NR(25) R(26), --CR(25)R(26)R(27);
- R(25) is --C.sub.f H.sub.2f --(C.sub.1 -C.sub.9)-heteroaryl,
- which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- f is zero, 1 or 2;
- R(26) and R(27)
- independently of one another are R(25), hydrogen or (C.sub.1 -C.sub.4)-alkyl; or
- R(1), R(2) and R(3)
- independently of one another are (C.sub.1 -C.sub.9)-heteroaryl N-oxide,
- which is linked via C or N and which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino; or
- R(1), R(2) and R(3)
- independently of one another are --SR(28), --OR(28), --NR(28)R(29) or --CR(28)R(29)R(30);
- R(28) is --C.sub.g H.sub.2g --(C.sub.1 -C.sub.9)-heteroaryl N-oxide,
- which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- g is zero, 1 or 2;
- R(29), R(30)
- independently of one another are defined as R(28), or are hydrogen or (C.sub.1 -C.sub.4)-alkyl; or
- R(1), R(2) and R(3)
- independently of one another are hydrogen, F, Cl, Br, I, --C.tbd.N, T--(CH.sub.2).sub.h --(C.sub.i F.sub.2i+1), R(31)SO.sub.l --, R(32)R(33)N--CO--, R(34)--CO-- or R(45)R(46)N--SO.sub.2, where the perfluoroalkyl group is straight-chain or branched;
- T is a bond, oxygen, --S-- or --NR(47);
- l is zero, 1 or 2;
- h is zero, 1 or 2;
- i is 1, 2, 3, 4, 5 or 6;
- R(31), R(32), R(34) and R(45)
- independently of one another are --(C.sub.1 -C.sub.8)-alkyl, --(C.sub.3 -C.sub.6)-alkenyl, (CH.sub.2).sub.n R(48) or --CF.sub.3 ;
- n is zero, 1, 2, 3 or 4;
- R(47) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
- R(48) is --(C.sub.3 -C.sub.7)-cycloalkyl or phenyl,
- which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, --CF.sub.3, methyl, methoxy and --NR(49)R(50);
- R(49) and R(50) are
- hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(32), R(34) and R(45) are hydrogen;
- R(33) and R(46)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(32) and R(33) and also R(45) and R(46)
- together are 5 or 6 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, --S--, --NH--, --NCH.sub.3 or --N-benzyl; or
- R(1), R(2) and R(3)
- independently of one another are R(51)--A--G--D--;
- R(51) is a basic protonatable radical, selected from the group consisting of an amino group --NR(52)R(53), an amidino group R(52)R(53)N--C{.dbd.N--R(54)}-- and a guanidino group R(52)R(53)N--C{.dbd.N--R(54)}--NR(55)--;
- R(52), R(53), R(54) and R(55)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(52) and R(53) are
- a group C.sub..alpha. H.sub.2.alpha. ;
- .alpha. is 4, 5, 6 or 7;
- where if .alpha.=5, 6 or 7 a carbon atom of the group C.sub..alpha. H.sub.2.alpha. can be replaced by a heteroatom groups, O, SO.sub.d or NR(56); or
- R(53) and R(54), or R(54) and R(55), or R(52) and
- R(55) are
- a group C.sub..gamma. H2.gamma.;
- .gamma. is 2, 3, 4 or 5;
- where if .gamma.=3, 4 or 5 a carbon atom of the group C.sub..gamma. H.sub.2.gamma. can be replaced by a heteroatom group O, SO.sub.d or NR(56);
- d is zero, 1 or 2;
- R(56) is hydrogen or methyl; or
- R(51) is a basic heteroaromatic ring system having 1-9 carbon atoms;
- A is a group C.sub.e H.sub.2e ;
- e is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
- where in the group C.sub.e H.sub.2e a carbon atom can be replaced by one of the groups --O--, --CO--, or --SO.sub.r --;
- r is zero, 1 or 2;
- G is a phenylene radical ##STR45## R(58) and R(59) independently of one another are hydrogen, methyl, methoxy, F, Cl, Br, I, CF.sub.3 or --SO.sub.s --R(60);
- s is zero, 1 or 2;
- R(60) is methyl or NR(61)R(62);
- R(61) and R(62)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
- D is --C.sub.v H.sub.2v --E.sub.w --;
- v is zero, 1, 2, 3 or 4;
- E is --O--, --CO--, --CH{OR(63)}--, --SO.sub.aa -- or --NR(63)--;
- w is zero or 1;
- aa is zero, 1 or 2
- R(63) is hydrogen or methyl; or
- R(1), R(2) and R(3)
- independently of one another are --CF.sub.2 R(64), --CF{R(65)}{R(66)}, --CF{(CF.sub.2).sub.q --CF.sub.3)}{R(65)}, --C{(CF.sub.2).sub.p --CF.sub.3 }.dbd.CR(65)R(66);
- R(64) is alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;
- R(65) and R(66) independently of one another are hydrogen or alkyl having 1, 2, 3, or 4 carbon atoms;
- q is zero, 1 or 2;
- p is zero, 1 or 2; or
- R(1), R(2) and R(3)
- independently of one another are --OR(67) or --NR(67)R(68);
- R(67) and R(68)
- independently of one another are hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms; or
- R(67) and R(68)
- together are 4, 5, 6 or 7 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, --S--, SO.sub.2, --NH--, --NCH.sub.3 or --N-benzyl;
- R(4) and R(5)
- independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, --OR(69), --NR(70)R(71) or --C.sub.z F.sub.2z+1 ;
- R(69), R(70) and R(71)
- independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
- z is 1, 2, 3 or 4;
- R(6) and R(7)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
- X is NR(72);
- R(72) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
- or a pharmaceutically tolerable salt thereof; but where compounds are excluded in which the radicals R(1) to R(7) and also R(72) are equal to hydrogen.
- 2. A compound of the formula I as claimed in claim 1, wherein:
- R(1), R(2) and R(3)
- independently of one another are --Y-{4-R(8)-phenyl}, --Y-{3-R(8)-phenyl} or --Y-{2-R(8)-phenyl},
- where the phenyl is in each case unsubstituted or substituted by a substituent from the group consisting of F, Cl, --CF.sub.3, methyl, methoxy and --NR(96)R(97);
- R(96) and R(97) independently of one another are hydrogen or --CH.sub.3 ;
- Y is a bond, oxygen, --S-- or --NR(9);
- R(9) is hydrogen or methyl;
- R(8) is SO.sub.a {NR(98)}.sub.b NR(99)R(10);
- a is 1 or 2;
- b is 0 or 1;
- a+b=2;
- R(98) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms or benzyl;
- R(99) and R(10)
- independently of one another are hydrogen, alkyl having 1 or 2 carbon atoms, benzyl, --(C.sub.2 -C.sub.3)-alkylene-NR(11)R(12), (C.sub.2 -C.sub.3)-alkylene-NR(13)--(C.sub.2 -C.sub.3)-alkylene-NR(37)R(38) or --(C.sub.0 -C.sub.2)-alkylene-CR(39)R(40)--CR(41)R(42)(C.sub.0 -C.sub.2)-alkylene-NR(43)-R(44);
- R(11), R(12), R(13), R(37), R(38), R(43) and R(44)
- independently of one another are hydrogen, methyl or ethyl;
- R(39), R(40), R(41) and R(42)
- independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or benzyl,
- where the phenyl is unsubstituted or substituted by a substituent selected from the group consisting of F,
- Cl, --CF.sub.3, methyl and methoxy; or
- R(99) and R(10)
- together are 4, 5 or 6 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, --S--, --NH-- or --NCH.sub.3 ; or
- R(8) is SO.sub.a {NR(98)}.sub.b NR(95)--C{.dbd.N--R(94)}--NR(93)R(92);
- R(95) is hydrogen;
- R(92), R(93) and R(94)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3)
- independently of one another are pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl,
- which are unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, Br, I, --CN, (C.sub.2 -C.sub.5)-alkanoyl, (C.sub.2 -C.sub.5)-alkoxycarbonyl, formyl, carboxyl, --CF.sub.3 and methyl; or
- R(1), R(2) and R(3)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3)
- independently of one another are --Q-4-{(CH.sub.2).sub.k --CH(NR(21)R(22))--(C.dbd.O)R(20)}-phenyl, --Q-3-{(CH.sub.2).sub.k --CH(NR(21)R(22))--(C.dbd.O)R(20)}-phenyl or --Q-2-{(CH.sub.2).sub.k --CH(NR(21)R(22))--(C.dbd.O)R(20)}-phenyl,
- where the phenyl in each case is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, --CF.sub.3, methyl, hydroxyl, methoxy and --NR(35)R(36);
- R(35) and R(36)
- independently of one another are hydrogen or --CH.sub.3 ;
- Q is a bond, oxygen, --S-- or --NR(18);
- R(1 8) is hydrogen or --(C.sub.1 -C.sub.4)-alkyl;
- R(21) and R(22)
- independently of one another are hydrogen, --(C.sub.1 -C.sub.5)-alkyl, --(C.sub.1 -C.sub.5)-alkanoyl, --(C.sub.1 -C.sub.5)-alkoxycarbonyl, benzyl or benzyloxycarbonyl; or
- R(21) is trityl;
- R(20) is --OR(23) or --NR(23)R(24);
- R(23) and R(24)
- independently of one another are hydrogen,
- --(C.sub.1 -C.sub.4)-alkyl or benzyl;
- k is zero, 1 or 2; or
- R(1), R(2) and R(3)
- independently of one another are (C.sub.1 -C.sub.9)-heteroaryl, which is linked via C or N and which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy and dimethylamino; or
- R(1), R(2) and R(3) are
- --SR(25), --OR(25), --NR(25)R(26), --CR(25)R(26)R(27);
- R(25) is --C.sub.f H.sub.2f --(C.sub.1 -C.sub.9)-heteroaryl,
- which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, dimethylamino;
- f is zero, 1 or 2;
- R(26) and R(27)
- independently of one another are defined as R(25) or are hydrogen or methyl; or
- R(1), R(2) and R(3)
- independently of one another are (C.sub.1 -C.sub.9)-heteroaryl N-oxide,
- which is linked via C or N and which is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino; or
- R(1), R(2) and R(3)
- independently of one another are --SR(28), --OR(28), --NR(28)R(29) or --CR(28)R(29)R(30);
- R(28) is --C.sub.g H.sub.2g --(C.sub.1 -C.sub.9)-heteroaryl N-oxide, which is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- g is zero or 1;
- R(29) and R(30)
- independently of one another are defined as R(28) or are hydrogen or methyl; or
- R(1),R(2) and R(3)
- independently of one another are hydrogen, F, Cl, CF.sub.3, R(31)SO.sub.2 --, R(32)R(33)N--CO--, R(34)--CO-- or R(45)R(46)N--SO.sub.2 ;
- R(31) and R(34)
- independently of one another are methyl or --CF.sub.3 ;
- R(32), R(33), R(45) and R(46)
- independently of one another are hydrogen or methyl; or
- R(1), R(2) and R(3)
- independently of one another are R(51)--A--G--D--;
- R(51) is --NR(52)R(53), an amidino group
- R(52)R(53)N--C{.dbd.N--R(54)}-- or a guanidino group R(52)R(53)N--C{.dbd.N--R(54)}--NR(55)--;
- R(52), R(53), R(54) and R(55)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(52) and R(53) are
- a group C.sub..alpha. H.sub.2.alpha. ;
- .alpha. is 4, 5, 6 or 7;
- where if .alpha.=5, 6 or 7 a carbon atom of the group C.sub..alpha. H.sub.2.alpha. can be replaced by a heteroatom group O, SO.sub.d or NR(56); or
- R(53) and R(54) are
- a group C.sub..gamma. H.sub.2.gamma. ;
- .gamma. is 2, 3, 4 or 5;
- where if .gamma.=3, 4 or 5 a carbon atom of the group C.sub..gamma. H.sub.2.gamma. can be replaced by a heteroatom group O, SO.sub.d or NR(56);
- d is zero or 2;
- R(56) is hydrogen or methyl; or
- R(51) is imidazolyl, pyridyl, quinolinyl or isoquinolinyl;
- A is a group C.sub.e H.sub.2e ;
- e is zero, 1, 2, 3, 4 or 5;
- where in the group C.sub.e H.sub.2e a carbon atom can be replaced by one of the groups --O--, --CO--, or --SO.sub.r --;
- r is zero or 2;
- G is a phenylene radical ##STR46## R(58) and R(59) independently of one another are hydrogen, methyl, F, Cl, CF.sub.3 or --SO.sub.2 --R(60);
- R(60) is methyl or NR(61)R(62);
- R(61) and R(62)
- independently of one another are hydrogen or methyl;
- D is --C.sub.v H.sub.2v --E.sub.w --;
- v is zero, 1, 2, 3 or 4;
- E is --O--, --CO--, --CH{OR(63)}--, --SO.sub.aa -- or --NR(63)--;
- w is zero or 1;
- aa is zero or 2
- R(63) is hydrogen or methyl; or
- R(2) is --CF.sub.2 R(64), --CF{R(65)}{R(66)}, --CF(CF.sub.3){R(65)},
- --C(CF.sub.3).dbd.CR(65)R(66);
- R(64) is alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;
- R(65) and R(66)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3)
- independently of one another are --OR(67) or --NR(67)R(68);
- R(67) and R(68)
- independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms; or
- R(67) and R(68)
- together are 4, 5 or 6 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, --S--, SO.sub.2, --NH-- or --NCH.sub.3 ;
- R(4) and R(5)
- independently of one another are hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, --OR(69), --NR(70)R(71) or --CF.sub.3 ;
- R(69), R(70) and R(71)
- independently of one another are hydrogen or methyl;
- R(6) and R(7)
- independently of one another are hydrogen or methyl;
- X is NR(72)
- R(72) is hydrogen or methyl.
- 3. A compound of the formula I as claimed in claim 1, wherein:
- R(1), R(2) and R(3)
- independently of one another are --O-{4-R(8)-phenyl},
- the phenyl in each case is unsubstituted or substituted by a substituent from the group consisting of F, Cl, --CF.sub.3, methyl and methoxy;
- R(8) is SO.sub.a {NR(98)}.sub.b NR(99)R(10);
- a is 1 or 2;
- b is 0 or 1;
- a+b=2;
- R(98) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
- R(99) and R(10)
- independently of one another are hydrogen, alkyl having 1 or 2 carbon atoms, benzyl, --(C.sub.2 -C.sub.3)-alkylene-NR(11)R(12), (C.sub.2 -C.sub.3)-alkylene-NR(13)--(C.sub.2 -C.sub.3)-alkylene-NR(37)R(38) or (C.sub.0 -C.sub.2)-alkylene-CR(39)R(40)-CR(41)R(42)(C.sub.0 -C.sub.2)-alkylene-NR(43)R(44);
- R(11), R(12), R(13), R(37), R(38), R(43) and R(44)
- independently of one another are hydrogen, methyl or ethyl;
- R(39), R(40), R(41) and R(42)
- independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or benzyl,
- where the phenyl is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, --CF.sub.3, methyl and methoxy; or
- R(99) and R(10)
- together are 4, 5 or 6 methylene groups, of which one CH.sub.2 group can be replaced by --NH-- or --NCH.sub.3 ; or
- R(8) is SO.sub.a {NR(98)}.sub.b NR(95)--C{.dbd.N--R(94)}--NR(93)R(92);
- R(95) is hydrogen;
- R(92), R(93) and R(94)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3)
- independently of one another are pyrrol-1-yl, which is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, Br, I, --CN, acetyl, (C.sub.2 -C.sub.5)-alkoxycarbonyl, --CF.sub.3 and methyl; or
- R(1), R(2) and R(3)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3)
- independently of one another are --Q-4-{(CH.sub.2).sub.k --CH(NR(21)R(22))--(C.dbd.O)R(20)}-phenyl,
- where the phenyl in each case is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, --CF.sub.3, methyl, hydroxyl and methoxy;
- Q is a bond or oxygen;
- R(21), R(22)
- independently of one another are hydrogen, methyl, --(C.sub.1 -C.sub.5)-alkanoyl, --(C.sub.1 -C.sub.5)-alkoxycarbonyl, benzyl or benzyloxycarbonyl;
- R(20) is --OR(23) or --NR(23)R(24);
- R(23), R(24)
- independently of one another are hydrogen, --(C.sub.1 -C.sub.4)-alkyl or benzyl;
- k is zero, 1 or 2; or
- R(1), R(2) and R(3)
- independently of one another are imidazolyl,
- which is linked via C or N and which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3 and methoxy; or
- R(1), R(2) and R(3) are
- --SR(25), --OR(25), --NR(25)R(26), --CR(25)R(26) R(27);
- R(25) is --(C.sub.1 -C.sub.9)-heteroaryl,
- which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3 and methoxy;
- R(26), R(27)
- independently of one another are hydrogen or methyl; or
- R(1), R(2) and R(3)
- independently of one another are --SR(28), --OR(28), --NR(28)R(29) or --CR(28)R(29)R(30);
- R(28) is --(C.sub.1 -C.sub.9)-heteroaryl N-oxide,
- which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3 and methoxy;
- R(29) and R(30)
- independently of one another are hydrogen or methyl; or
- R(1), R(2) and R(3)
- independently of one another are hydrogen, F, Cl, CF.sub.3, R(31)SO.sub.2 --R(32)R(33)N--CO--, R(34)--CO-- or R(45)R(46)N--SO.sub.2 ;
- R(31) and R(34)
- independently of one another are methyl or --CF.sub.3 ;
- R(32), R(33), R(45) and R(46)
- independently of one another are hydrogen or methyl; or
- R(2) is R(51)--A--G--D--;
- R(51) is --NR(52)R(53), an amidino group
- R(52)R(53)N--C{.dbd.N--R(54)}-- or a guanidino group R(52)R(53)N--C{.dbd.N--R(54)}--NR(55)--;
- R(52), R(53), R(54) and R(55)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(52) and R(53) are
- a group C.sub..alpha. H.sub.2.alpha. ;
- .alpha. is 4, 5, 6 or 7;
- where if .alpha.=5, 6 or 7 a carbon atom of the group C.sub..alpha. CH.sub.2.alpha. can be replaced by a heteroatom group O, SO.sub.d or NR(56); or
- R(53) and R(54) are
- a group C.sub..gamma. H.sub.2.gamma. ;
- .gamma. is 2, 3, 4 or 5;
- where if .gamma.=3, 4 or 5 a carbon atom of the group C.sub.65 H.sub.2.gamma. can be replaced by a heteroatom group O, SO.sub.d or NR(56);
- d is zero or 2;
- R(56) is hydrogen or methyl; or
- R(51) is imidazolyl, pyridyl, quinolinyl or isoquinolinyl;
- A is C.sub.e H.sub.2e ;
- e is zero, 1, 2, 3, 4 or 5;
- where in the group C.sub.e H.sub.2e a carbon atom can be replaced by one of the groups --O--, --CO--, or --SO.sub.r --, --NR(57)--, --NR(57)--CO--;
- r is zero or 2;
- G is a phenylene radical ##STR47## R(58) and R(59) independently of one another are hydrogen, methyl, F, Cl, CF.sub.3 or --SO.sub.2 --R(60);
- R(60) is methyl or NR(61)R(62);
- R(61) and R(62)
- independently of one another are hydrogen or methyl;
- D is --C.sub.v H.sub.2v --E.sub.w --;
- v is zero, 1, 2, 3 or 4;
- E is --O--, --CO--, --CH{OR(63)}--, --SO.sub.aa -- or --NR(63)--;
- w is zero or 1;
- aa is zero or 2
- R(63) is hydrogen or methyl, or
- (2) is --CF.sub.2 R(64), --CF{R(65)}{R(66)}, --CF(CF.sub.3){R(65)}, --C(CF.sub.3).dbd.CR(65)R(66);
- R(64) is alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;
- R(65) and R(66)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3)
- independently of one another are --OR(67) or --NR(67)R(68);
- R(67) and R(68)
- independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms; or
- R(67) and R(68)
- together are 4, 5 or 6 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, --S--, SO.sub.2, --NH-- or --NCH.sub.3 ;
- R(4) and R(5)
- independently of one another are hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, --OR(69), --NR(70)R(71) or --CF.sub.3 ;
- R(69), R(70) and R(71)
- independently of one another are hydrogen or methyl;
- R(6) and R(7)
- independently of one another are hydrogen or methyl;
- X is NR(72)
- R(72) is hydrogen or methyl.
- 4. A compound of the formula I as claimed in claim 1, wherein:
- R(2) is --Q-{4-R(8)-phenyl},
- R(8) is SO.sub.a {NR(98)}.sub.b NR(99)R(10);
- a is 1 or 2;
- b is 0 or 1;
- a+b=2;
- R(98) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
- R(99) and R(10)
- independently of one another are hydrogen, alkyl having 1 or 2 carbon atoms, --(C.sub.2 -C.sub.3)-alkylene-NR(11)R(12);
- R(11) and R(12)
- independently of one another are hydrogen, methyl or ethyl; or
- R(99) and R(10)
- together are 5 or 6 methylene groups, of which one CH.sub.2 group can be replaced by --NH-- or --N--CH.sub.3 ; or
- R(8) is SO.sub.a {NR(98)}.sub.b NR(95)--C{.dbd.N--R(94)}--NR(93)R(92);
- R(95) is hydrogen;
- R(92), R(93) and R(94)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1) is pyrrol-1-yl,
- which is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, Br, I, --CN, acetyl, --CF.sub.3 and methyl; or
- R(1), R(2) and R(3)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(2) is --O-4-{CH.sub.2 --CH(NR(21)R(22))--(C.dbd.O)R(20)}-phenyl,
- R(21) and R(22)
- independently of one another are hydrogen, methyl, --(C.sub.1 -C.sub.5)-alkanoyl, --(C.sub.1 -C.sub.5)-alkoxycarbonyl, benzyl, benzyloxycarbonyl;
- R(20) is --OR(23) or --NR(23)R(24);
- R(23) and R(24)
- independently of one another are hydrogen or --(C.sub.1 -C.sub.4)-alkyl; or
- R(2) is imidazolyl, which is linked via C or N; or
- R(2) is --SR(25) or --OR(25);
- R(25) is pyridyl, quinolinyl or isoquinolinyl, which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3 and methoxy; or
- R(2) is --SR(28) or --OR(28);
- R(28) is pyridyl N-oxide, quinolinyl N-oxide or isoquinolinyl N-oxide, which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3 and methoxy; or
- R(1) is hydrogen, F, Cl, CF.sub.3, R(31)SO.sub.2 --, or R(45)R(46)N--SO.sub.2 ;
- R(31) is methyl or --CF.sub.3 ;
- R(45) and R(46)
- independently of one another are hydrogen or methyl; or
- R(2) is R(51)--A--G--O--;
- R(51) is --NR(52)R(53);
- R(52) and R(53)
- independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms; or
- R(52) and R(53) are
- C.sub..alpha. H.sub.2.alpha. ;
- .alpha. is 5 or 6;
- where a carbon atom of the group C.sub.a H.sub.2.alpha. can be replaced by NR(56);
- R(56) is hydrogen or methyl; or
- R(51) is imidazolyl, pyridyl, quinolinyl or isoquinolinyl;
- A is C.sub.e H.sub.2e ;
- e is zero, 1, 2 or 3;
- where in the group C.sub.e H.sub.2e a carbon atom can be replaced by one of the groups --O--, or --SO.sub.r --;
- r is zero or 2;
- G is a phenylene radical ##STR48## or R(2) is --CF.sub.2 R(64), --CF{R(65)}{R(66)}, --CF(CF.sub.3){R(65)}, --C(CF.sub.3).dbd.CR(65)R(66);
- R(64) is alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 5 or 6 carbon atoms;
- R(65) and R(66)
- independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
- R(1), R(2) and R(3)
- independently of one another are --OR(67) or --NR(67)R(68);
- R(67) and R(68)
- independently of one another are hydrogen, methyl or ethyl; or
- R(67) and R(68)
- together are 4-5 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, --NH-- or --NCH.sub.3 ;
- R(4) and R(5)
- independently of one another are hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, or --CF.sub.3 ;
- R(6) and R(7)
- independently of one another are hydrogen or methyl;
- X is NR(72);
- R(72) is hydrogen or methyl.
- 5. A process for preparing a compound of the formula I as claimed in claim 1, which comprises
- reacting with a guanidine a compound of the formula IV ##STR49## in which R(1) to R(7) and X have the meanings given in claim 1, and in which L' is chlorine, ethoxy, isobutoxy, benzotriazol-1-oxy or 1-imidazolyl.
- 6. A method for the treatment of an arrhythmia, comprising administering to a host in need of the treatment an effective amount of a compound of claim 1.
- 7. A method for the treatment or prophylaxis of cardiac infarct, comprising administering to a host in need of the treatment or prophylaxis an effective amount of a compound of claim 1.
- 8. A method for the treatment or prophylaxis of angina pectoris, comprising administering to a host in need of the treatment or prophylaxis an effective amount of a compound of claim 1.
- 9. A method for the treatment or prophylaxis of an ischemic condition of the heart, comprising administering to a host in need of the treatment or prophylaxis an effective amount of a compound of claim 1.
- 10. A method for the treatment or prophylaxis of an ischemic condition of the peripheral and central nervous system and of stroke, comprising administering to a host in need of the treatment or prophylaxis an effective amount of a compound of claim 1.
- 11. A method for the treatment or prophylaxis of an ischemic condition of a peripheral organs or limb, comprising administering to a host in need of the treatment or prophylaxis an effective amount of a compound of claim 1.
- 12. A method for the treatment of a state of shock, comprising administering to a host in need of the treatment an effective amount of a compound of claim 1.
- 13. A method for protecting an organ during a surgical operation or an organ transplant comprising applying to the organ an effective amount of a compound of claim 1.
- 14. A method for the preservation or storage of a transplant for surgical measures comprising applying to the transplant an effective amount of a compound of claim 1.
- 15. A method for the treatment of a disease in which cell proliferation is a primary or secondary cause, comprising administering to a host in need of the treatment an effective amount of a compound of claim 1.
- 16. A method for the diagnosis of hypertension or a proliferative disorder, comprising administering to a host to be diagnosed a compound of claim 1 as a diagnostic agent for the inhibition of a cellular Na.sup.+ /H.sup.+ exchanger.
- 17. A pharmaceutical composition comprising a compound of claim 1, together with a physiologically acceptable carrier.
- 18. A compound of the formula I as claimed in claim 1, selected from the group consisting of 3-bromo-5-fluorobenzylaminocarbonylguanidine hydrochloride; 3,5-dimethylbenzylaminocarbonylguanidine hydrochloride; 2-fluorobenzylaminocarbonylguanidine hydrochloride; 3-fluorobenzylaminocarbonylguanidine hydrochloride; 2,6-difluorobenzylaminocarbonylguanidine hydrochloride; 2,5-difluorobenzylaminocarbonylguanidine hydrochloride; 3-fluoro-5-trifluoromethylbenzylaminocarbonylguanidine hydrochloride; 4-dimethylaminobenzylaminocarbonylguanidine hydrochloride; 3,5-difluorobenzylaminocarbonylguanidine hydrochloride; 3-methylbenzylaminocarbonylguanidine hydrochloride; N-3,5-difluorobenzyl-N-methylaminocarbonylguanidine hydrochloride; N-(3,4-dichlorobenzyl)-N-methylaminocarbonylguanidine hydrochloride; benzylaminocarbonylguanidine hydrochloride; N-(2-chloro-5-trifluoromethylbenzyl)-N-methylaminocarbonylguanidine hydrochloride; N-methyl-N-(3-methylsulfonyl-4-phenoxybenzyl)aminocarbonylguanidine methanesulfonate; N-methyl-N-(3-methylsulfonyl-4-isopropylbenzyl)aminocarbonylguanidine methanesulfonate; and N-(4-fluoro-3-trifluoromethylbenzyl)-N-methylaminocarbonylguanidine hydrochloride.
- 19. A method for the treatment of an arrhythmia, which comprises administering to a host in need of such treatment an effective amount of a pharmaceutical composition as claimed in claim 17.
- 20. The method as claimed in claim 15, wherein the disease is atherosclerosis, a diabetic late complication, a carcinomatous disorder, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, or prostate hyperplasia.
Priority Claims (1)
Number |
Date |
Country |
Kind |
195 18 073 |
May 1995 |
DEX |
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Parent Case Info
This is a is a division of application Ser. No. 08/648,499, filed May 15, 1996, now U.S. Pat. No. 5,783,710, the entire contents of which are incorporated herein by reference.
US Referenced Citations (4)
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Entry |
Krug, et al., "Pochodne Guanidyny. II*, Nowe Metody Otrzymywania Niektorych Acylopochodnych Guanidyny," Roczniki Chemii. vol. 41, pp. 1087-1091, 1967. |
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Divisions (1)
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Number |
Date |
Country |
Parent |
648499 |
May 1996 |
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